2XOT

Crystal structure of neuronal leucine rich repeat protein AMIGO-1

Summary for 2XOT

• Entry DOI: 10.2210/pdb2xot/pdb
• Descriptor: Amphoterin-induced protein 1, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: cell adhesion, neuronal protein, neurite growth regulation
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 2
• Total formula weight: 83652.64

Authors

Kajander, T.,Kuja-Panula, J.,Rauvala, H.,Goldman, A. (deposition date: 2010-08-23, release date: 2011-09-21, Last modification date: 2024-11-13)

Primary citation

Kajander, T.,Kuja-Panula, J.,Rauvala, H.,Goldman, A.
Crystal Structure and Role of Glycans and Dimerisation in Folding of Neuronal Leucine-Rich Repeat Protein Amigo-1
J.Mol.Biol., 413:1001-, 2011

PubMed Abstract: AMIGO-1 is the parent member of a novel family of three cell surface leucine-rich repeat (LRR) proteins. Its expression is induced by the binding of HMGB1 (high-mobility group box 1 protein) to RAGE (receptor for advanced glycation end products) on neurons. Binding of HMGB1 to RAGE is known to have a direct effect on cellular growth regulation and mobility, and AMIGO-1 directly supports growth of neuronal processes and fasciculation of neurites. In addition, the second member of the AMIGO-family, AMIGO-2, has been implicated in adhesion of tumor cells in adenocarcinoma and survival of neurons. We have determined the crystal structure of AMIGO-1 at 2.0 Å resolution, which reveals a typical cell surface LRR domain arrangement with N- and C-terminal capping domains with disulfide bridges, followed by a C2-type Ig domain. AMIGO-1 is a dimer, with the LRR regions forming the dimer interface, and sequence conservation analysis and static light-scattering measurements suggest that all three AMIGO family proteins form similar dimers. Based on the AMIGO-1 structure, we have also modeled AMIGO-2 and present small-angle X-ray scattering data on AMIGO-2 and AMIGO-3. Our mutagenesis studies show that AMIGO-1 dimerization is necessary for proper cell surface expression and thus probably for proper or stable folding in the endoplastic reticulum and for the function of the protein. Based on the data presented earlier, we also suggest that dimerization through the LRR-LRR interface is likely to be involved in cell-cell adhesion by AMIGO-1, while extensive glycosylation may have a role.

PubMed: 21983541
DOI: 10.1016/J.JMB.2011.09.032

Experimental method

X-RAY DIFFRACTION (2 Å)